Proteomics and the Warrior King

Friday, August 17, 2018

The warrior king of Sparta, King Leonidas, and his small legion found themselves arrayed against an army of hundreds of thousands. Though they fought bravely until the very end, the odds and ultimately the Fates did not favor the poor king and his legion in that gory battle of Thermopylae.

Such battles are waged not just historically, but also today, though in much tinier, subcellular arenas. Consider Duchenne muscular dystrophy (DMD), a disease that predominantly affects young men. The origins of the battle start at the genetic level (National Institutes of Health (NIH), 2018). Mutations in the DMD gene, which can happen sporadically or be inherited on the X chromosome, compromise the critical protein dystrophin. According to the NIH’s war reports, dystrophin plays a primary role in stabilizing and guarding muscle fibers. Losing it leads to a constant attack on muscle tone and integrity, and ultimately to muscle defeat.

Further reading of the NIH’s war reports supplies added details. Early on in the battle, the brave young warriors bear the full brunt of the attack. Although their muscles struggle mightily to maintain themselves, children with DMD experience mobility problems early. Their calf muscles become enlarged as fat cells and other tissue replace the muscle. Over time, this muscle destruction becomes widespread, leading to breathing difficulties, joint problems and enlarged hearts (cardiomyopathy). In addition to compromised bodies, the battle also wreaks havoc on their minds, burdening the warriors with cognitive impairment, communication problems and impaired social behavior. Like the valiant King Leonidas and his army, these modern warriors are doomed.

But maybe we can delay or even change the fate of current or future warriors. Maybe there are additional weapons we have not considered. For example, in a piece of intel we learn that dystrophin is important not only to muscle formation, but also to signaling (i.e., communications between cells), and disruption of communications could be contributing to the disease (Allen, Whitehead, & Froehner, 2016). The intel’s authors postulate that a deeper understanding about the disruption in communications could open the door for more therapeutics as well as improvements in diagnosis, checking disease progression and assessing the effectiveness of treatments (Allen et al., 2016).

The SOMAscan platform, a proteomic technology, has been enlisted in battle against the tragic disease. The technology revealed that as few as six proteins maybe needed to accurately diagnose the disease (Parolo et al., 2018). Proteomics also revealed that DMD altered the communications in the immune system, the neurotrophin signaling pathway, apoptosis (cell death) and additional effectors of other biological systems (Parolo et al., 2018).

Once diagnosed, it becomes imperative to continue surveillance of the disease’s progression. One way to monitor progression involves invasive muscle biopsies. Recently, researchers developed a new less invasive way to monitor the progression using the SOMAscan platform, and it only requires a blood sample (Spitali et al., 2018). Over time, the tests revealed that the levels of hundreds of proteins changed, which could be indicative of muscle deterioration, increase of fat cells and heart problems (Spitali et al., 2018). Another group used the SOMAscan platform to identify biomarkers for cardiomyopathy in DMD patients (Anderson et al., 2017).

The war of the ages continues, but it may not last forever. As mentioned, proteomics can reveal the weaknesses of the DMD enemy and the effects of therapeutic strategies at the molecular level (Hathout et al., 2016). Let us hope that with different tactics, the fates may start to favor the brave and valiant warriors.

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